These studies investigate the biosynthesis, utilization and metabolism of heme, and the regulation of hemoprotein function in mammalian tissues, particularly the factors affecting the regulation of heme and hemoprotein levels at different stages of development and during chronic disease processes. Elucidation of alterations in heme biosynthetic pathway enzymes and in urinary concentrations of heme precursors incurred by exposure to hematotoxic environmental agents are of special interest. Substances under current investigation include various trace metal and TCDD. Present studies suggest that the regulation of heme biosynthesis and metabolism in various tissues is exquisitely sensitive to alteration by a variety of environmentally important metals. Patterns of blood and urinary porphyrins resulting from exposure to these agents may permit non-invasive means for assessing pretoxic exposure to metals in humans, or serve as models for defining the etiology of inherited or drug-induced porphyrias. Other studies are designed to assess the effects of impaired heme biosynthesis on microsomal hemoprotein function resulting from exposure to a variety of environmental hematotoxic agents.